The Red Devils, winners of the competition in 2016-17, topped their Europa League pool, losing just once with a youthful side at Astana.
Struggling Arsenal will have been eyeing a more favorable draw than Olympiacos, who are familiar with north London having faced Tottenham in the Champions League.
Inter were unfortunate not to make the last 16 of the Champions League, losing out to Barcelona and Borussia Dortmund, but Antonio Conte's side will fancy their chances against Bulgarian side Ludogorets.
Sevilla, who are the competition's most successful club, with five wins across the UEFA Cup and Europa League, will have to overcome Cluj to make the last 16.
Old Firm duo Celtic and Rangers take on Copenhagen and Braga, while Premier League side Wolves lock horns with LaLiga strugglers Espanyol.
Ajax, Champions League semi-finalists last season, also face Spanish opposition in the form of Getafe, and Roma – who reached the last four of Europe's premier competition in 2017-18 – go up against Gent.
Bayer Leverkusen take on two-time winners Porto in one of the round's stand-out ties, as Shakhtar Donetsk and Benfica – two demoted Champions League outfits – face off.
Having impressed against Liverpool and Napoli, Salzburg play Eintracht Frankfurt.
First-leg games take place on February 20, with the return fixtures a week later.